Background Primary Sjögren’s syndrome (SS) is characterized by an increased risk of lymphoma in patients with prelymphomatous manifestations (i.e., myoepithelial sialadenitis (MESA) or mixed cryoglobulinemia). Increased levels of B-lymphocyte stimulator (BLyS) characterize different autoimmune diseases, and in particular SS.
Objectives Serum BLyS levels in SS-related B-cell lymphoproliferative disorders were studied, by integrating the results with the disease activity score and molecular analyses of B-cell expansion on the salivary glands.
Methods 76 primary SS patients were studied. SS patients were distributed into four groups: a) SS without any lymphoproliferative disorder (n=34); b) SS with cryoglobulinemic vasculitis (CV) without overt lymphoma (n=14); c) SS with MESA (n=12); d) SS with overt lymphoma (n=16). Serum BLyS and molecular analyses of B cells in the salivary gland tissues, when available, were performed. Patients with SS and persistent parotid swelling underwent parotid biopsy.
Results BLyS differed between SS subgroups, higher levels being documented in patients with B-cell lymphoproliferative disorders (as a whole group) versus SS without (1.85 (0.45-4.12) ng/ml vs 1.12 (0.56-1.98) ng/ml; p<0.0001), and a significant difference was also observed between SS with frank lymphoma and SS without any lymphoproliferative disorder (p=0.0002). BLyS levels significantly correlated with the EULAR SS disease activity index (ESSDAI) (r=0.62, p<0.0001, Spearman’s test). Higher ESSDAI scores were observed in SS with overt lymphoma if compared with SS without a lymphoproliferative disorder [22.5 (16-35) vs 4.0 (0-16), p<0.0001], or if compared with SS with CV [22.5 (16-35) vs 15.5 (7-25), p=0.005], who showed an intermediate result. Clonal B-cell expansion in the salivary glands rather than polyclonal B-cell expansion was associated with higher BLyS levels [1.98 (0.45-4.12) vs 1.15 (0.56-3.25) ng/ml; p=0.013)]. ESSDAI score was also significantly associated with B-cell clonal expansion in the salivary glands [21.0 (0-35) vs 6.0 (0-37), p=0.0003] and this association was confirmed even after excluding SS patients with lymphoma [17.5 (0-35) vs 6.0 (0-37), p=0.02].
Conclusions Higher BLyS levels and clonal B-cell expansion characterizes SS with B-cell lymphoproliferative disorders, even at pre-lymphomatous stages. This subgroup of SS patients showed the highest ESSDAI scores. This is the biologic rationale for targeting both the clonal B-cell expansion and the BLyS overproduction in SS patients with a B-cell lymphoproliferative disorder and high disease activity.
Disclosure of Interest None Declared